Minding the dynamic gap: measuring ultrafast processes in biomolecular systems

Biological processes in vivo involve interactions between large, complex molecules under conditions that are best-approximated by a viscous, multicomponent solution at temperatures often somewhat above room temperature. This means that the molecules involved are dynamic --- their structure changes --- on many timescales in ways that range from very small, localized fluctuations to fundamental changes in their overall appearance. What roles do these dynamics play in the structure–function relationship? Do very fast, local motions have any impact on well-characterized, slower structure changes? How do we go about measuring the very fastest biomolecular fluctuations to find out? Here we discuss ultrafast multidimensional (2D-IR) spectroscopy and look at the complementary information that it provides as part of a raft of biophysical experiments.